| 1. |
- Carlstedt, F., et al.
(författare)
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Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department
- 1997
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 27:12, s. 977-981
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Tidskriftsartikel (refereegranskat)abstract
- Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg ml-1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non-survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Cox's proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.
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| 2. |
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| 3. |
- Eriksson, Barbro, et al.
(författare)
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Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors
- 1990
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Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 65:9, s. 1883-1890
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Tidskriftsartikel (refereegranskat)abstract
- A prospective study was performed on 84 patients with neuroendocrine pancreatic tumors. Fifty-nine (70%) had malignant tumors and received causal medical treatment. Streptozotocin in combination with 5-fluorouracil or doxorubicin was used as first-line treatment and produced overall objective responses in 20 of 44 (45%) patients with a median duration of response of 27.5 months. Thirty-two patients who failed on chemotherapy subsequently received interferon treatment and 20 (63%) responded objectively with a median duration of 20.5 months. Octreotide, third-line treatment in 14 patients, produced objective responses in four patients (28%) (median duration of response, 16 months). The median survival from diagnosis in malignant cases was 6.7 years. Even if none of the current medical therapies are curative for patients with malignant endocrine pancreatic tumors, a prolonged survival would be observed during the last decade. Since the age at diagnosis has not been dramatically reduced despite improvements in diagnostic methods, the prolonged survival might be attributed to causal medical treatment.
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| 4. |
- Eriksson, Barbro, et al.
(författare)
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Neuroendocrine pancreatic tumours : clinical presentation, biochemical and histopathological findings in 84 patients
- 1990
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 228:2, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 3 5 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominalsymptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.
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| 5. |
- Eriksson, Karin, et al.
(författare)
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Gonadotropin Glycoforms Circulating in Women Using Progestins of the Levonorgestrel Family for Contraception
- 2020
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Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- Context: The progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women. One contraceptive effect of these progestins is inhibition of ovulation, which may be a result of changes in gonadotropin glycosylation patterns. Gonadotropin glycoforms differ in number of glycans and bioactivity: more bioactive low-N-glycosylated glycoforms, diglycosylated luteinizing hormone (LHdi) and triglycosylated follicle-stimulating hormone (FSHtri), and less bioactive fully N-glycosylated glycoforms, LHtri and FSHtetra.Objective: Characterize the glycosylation patterns on the circulating gonadotropin glycoforms in women using 13-ethylgonane progestins for contraception.Design Subjects Main Outcome Measures: Serum samples, collected from 92 healthy women using 13-ethylgonane progestins for contraception, were included. Forty women used progestin-only continuously and 52 used progestins combined with ethinylestradiol (EE) for 3 weeks followed by a hormone-free week. Concentration, sulfonation, and sialylation of each glycoform were determined and compared with follicular phase values of normal menstrual cycles.Results: The progestin-only group had significantly increased serum levels, decreased sulfonation, and increased sialylation of LHdi. The LHdi/FSHtri ratio was increased. The progestin+EE group had significantly decreased gonadotropin glycoform concentrations and decreased sialylation of FSHtri. The progestin+EE effect on sialylation of FSHtri occurred later during the treatment cycle in contrast to the effect on FSHtri concentration.Conclusions: The 2 different progestin treatments induced different effects on the glycan synthesis and concentrations of more bioactive low-glycosylated gonadotropins. Progestin-only treatment increased sialylation and decreased sulfonation of LHdi molecules, contributing to sustained higher levels of bioactive LHdi molecules. Progestin+EE treatment decreased sialylation of FSHtri, contributing to a shorter half-life and decreased levels of bioactive FSHtri.
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| 6. |
- Hobson, Bruce, et al.
(författare)
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A comparison between chorionic gonadotrophins extracted from human, rhesus monkey and marmoset placentae
- 1972
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 55:2, s. 363-368
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Tidskriftsartikel (refereegranskat)abstract
- Evidence is provided to show that chorionic gonadotrophins extracted from the human, rhesus monkey and marmoset placentae have antigenic determinants in common. Similar slopes were obtained for these gonadotrophins in a radioimmunoassay for human chorionic gonadotrophin (HCG). The biological activity of the monkey gonadotrophins was neutralized by anti-HCG serum. When the gonadotrophic activity of the monkey placental extracts was assayed biologically and immunologically, using HCG as a standard, similar results were obtained. Higher values were obtained by the immunoassay than by the bioassay when extracts of human placenta were assayed using the same HCG standard.
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| 7. |
- Holmberg, Lars, et al.
(författare)
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Pre-operative oestradiol levels - relation to survival in breast cancer
- 2001
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 27:2, s. 152-156
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: There are clinical observations that operation during the luteal phase of the menstrual cycle (with high oestradiol levels) may positively influence prognosis in breast cancer. However, few studies have information on plasma levels of hormones pre-operatively. METHODS: We studied 774 women treated for breast cancer where plasma levels of oestradiol had been measured 1-2 days pre-operatively. Date and cause of death were ascertained from the files of the Swedish Cancer Register and 5434 person-years were observed. The endpoint was death with breast cancer as the underlying cause (n=41 and n=158 in the pre- and post-menopausal group, respectively). RESULTS: In life-table analyses, only pre-menopausal patients with oestradiol 500 pmol/l and above had a tendency (not statistically significant) for better survival. Multivariate Cox models with oestradiol modelled in continuous form yielded relative hazards (RH) close to unity in all women and in strata according to menopausal status. CONCLUSIONS: When oestradiol was analysed in categorized form, only women with the highest levels had a tendency for improved prognosis (RH around 0.7; not statistically significant). Moreover, this pattern was not apparent for pre-menopausal women. Our findings contradict the notion that the pre-operative oestradiol level is independently associated with breast cancer prognosis.
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| 8. |
- Lambe, Mats, et al.
(författare)
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Ethnic differences in breast cancer risk : a possible role for pregnancylevels of alpha-fetoprotein?
- 2003
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Ingår i: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 14:1, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer incidence rates are up to five times higher in white women in the United States compared with Asian women in China and Japan. A search for factors that modify estrogen's biological effect differentially between ethnic groups may add to the understanding of international variations in breast cancer risk. Recent evidence indicates that alpha-fetoprotein, a glycoprotein produced by the fetal liver, has important antiestrogenic properties. During pregnancy, alpha-fetoprotein reaches peak concentrations in maternal serum during the third trimester. METHODS: We compared pregnancy levels of alpha-fetoprotein in a population with high risk of breast cancer (Boston, MA) and low risk (Shanghai, China). Blood samples were collected around the 16th week and around the 27th week of gestation among women enrolled from March 1994 to October 1995. The number of specimens available for alpha-fetoprotein analysis was 1,033. RESULTS: Alpha-fetoprotein levels, adjusted for gestational length, were substantially higher in Shanghai compared with Boston women at both time points. When adjustments were made for prepregnancy weight, parity, offspring's sex and maternal age, alpha-fetoprotein levels remained 13% higher in Shanghai at 16 weeks of pregnancy but not at 27 weeks. CONCLUSIONS: These findings may explain, at least in part, the difference in breast cancer risk between Chinese and American women. On the population level, alpha-fetoprotein may influence risk by modifying the effect of biologically active estrogens both in the mother and in female offspring.
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| 9. |
- Lipworth, L., et al.
(författare)
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Maternal pregnancy hormone levels in an area with a high incidence (Boston, USA) and in an area with a low incidence (Shanghai, China) of breast cancer
- 1999
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 79:1, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Characteristics probably associated with the fetal hormonal milieu have recently been shown to increase (birth size indicators, prematurity, neonatal jaundice) or decrease (pregnancy toxaemia) breast cancer risk in the female offspring. However, it is unknown whether differences in pregnancy hormone levels may contribute to the marked geographical variation in breast cancer incidence. We have compared, in a highly standardized manner, pregnancy hormone levels in a population with high incidence and one with low incidence of breast cancer. Three hundred and four pregnant Caucasian women in Boston and 334 pregnant Chinese women in Shanghai were enrolled from March 1994 to October 1995. Levels of oestradiol, oestriol, prolactin, progesterone, human growth hormone, albumin and sex hormone-binding globulin were measured in maternal blood at weeks 16 and 27 of gestation and compared between the two study sites using non-parametric Wilcoxon's rank-sum test. Demographical, anthropometrical and pregnancy characteristics were ascertained through interview, and relevant variables concerning delivery and the newborn were abstracted from medical records and paediatric charts. During the first visit, median serum levels of all studied hormones were statistically significant, and in most instances substantially, higher among Chinese women, who have a low incidence of breast cancer, compared with American women, who have a high incidence of breast cancer. An analogous pattern was evident during the second visit, although the relative differences tended to be smaller. Further research is needed to identify lifestyle or other exogenous determinants of pregnancy hormone levels, as well as possible mechanisms by which they may influence carcinogenic processes in the breast and possibly other organs.
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| 10. |
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| 11. |
- Skogseid, Britt, et al.
(författare)
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Multiple endocrine neoplasia type 1 : a ten year prospective screening study in four kindreds
- 1991
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 73:2, s. 281-287
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Tidskriftsartikel (refereegranskat)abstract
- A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified.
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| 12. |
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| 13. |
- Wide, Leif, et al.
(författare)
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A solid phase radioimmunoassay method for ferritin in serum using (125)I-labelled ferritin
- 1977
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 82:1, s. 15-19
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Tidskriftsartikel (refereegranskat)abstract
- A solid phase radioimmunoassay method for ferritin in serum was developed using ferritin conjugated with an (125)I-labelled ester. The method was based upon competitive inhibition utilizing the free antigen-binding sites of antibodies to ferritin bound to a ferritin which had been chemically coupled to insoluble polysaccharide particles. The method was evaluated with regard to specificity, sensitivity, precision and practicability and was found to be a robust method suitable for the assay of ferritin in human serum in clinical studies. There was a significant (P<0.001) difference between the ferritin levels in healthy men and women, mean values 100 and 66 arb U/l respectively. Male blood donors had significantly (P<0.002) lower ferritin levels in serum (mean 68.5 arb U/l) than other healthy men. Patients with iron overload or hepatic damage had high values, as expected, and the serum levels of ferritin reflected changes in iron deposits during phlebotomy and iron treatment in 3 healthy men.
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| 14. |
- Wide, Leif, et al.
(författare)
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Determination of Half-lives of Circulating FSH and LH Glycoforms in Women During GnRH Receptor Blockade
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:10, s. e4058-e4062
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Both FSH and LH circulate as 2 glycoforms, differing in number of glycans: low-N-glycosylated glycoforms, FSHtri and LHdi, and fully N-glycosylated glycoforms, FSHtetra and LHtri.OBJECTIVES: To determine the half-lives of endogenous circulating gonadotropin glycoforms in women during GnRH receptor blockade.DESIGN/PARTICIPANTS: Serum samples were collected in 8 healthy women before and up to 20 hours after administration of the NAL-GLU GnRH antagonist. Three women were in early follicular phase, 2 at mid-cycle phase, and 3 were postmenopausal.MAIN OUTCOME MEASURES: The half-life of each glycoform was estimated by monoexponential decay for FSH (n = 8) and LH (n = 5). Data were analyzed using paired t tests.RESULTS: Half-lives in the circulation of low-N-glycosylated glycoforms of both FSH and LH were shorter than those of the fully N-glycosylated glycoforms (mean; range, FSHtri 343; 116-686 minutes vs FSHtetra 757; 436-1038, minutes, P = 0.0003; LHdi 125, 84-198 minutes vs LHtri 164, 107-235 minutes, P = 0.004). The half-lives of low-and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH glycoforms, P = 0.0008.CONCLUSIONS: For both FSH and LH, low-N-glycosylated glycoforms disappeared from the circulation faster than the fully N-glycosylated. The half-lives of low and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH. The estimated values for half-life in the circulation of total FSH and total LH will depend on the relative amounts of the 2 glycoforms of each hormone and their individual disappearance rates in circulation.
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| 15. |
- Wide, Leif, et al.
(författare)
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Dynamic changes in glycosylation and glycan composition of serum FSH and LH during natural ovarian stimulation
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:3, s. 153-164
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Tidskriftsartikel (refereegranskat)abstract
- Background. Glycosylation and glycan composition are of fundamental importance for the biological properties of FSH and LH. The aim of this study was to determine the glycosylation, sialylation, and sulfonation of serum FSH and LH throughout the normal menstrual cycle. Methods. Serum samples were collected from 79 healthy women with regular menstrual cycles. The mean numbers of anionic monosaccharide (AMS), sialic acid (SA), and sulfonated N-acetylgalactosamine (SU) residues per FSH and LH molecule were estimated for all sera with methods based on electrophoreses, neuraminidase treatments, and fluoroimmunoassays of the gonadotrophins. Results. Di-glycosylated glycoforms (FSHdi, LHdi) were detected in serum in addition to tetra-glycosylated FSH (FSHtetra) and tri-glycosylated LH (LHtri). FSHdi exhibited two peaks: one on day 5 to 7 and one, more pronounced, at midcycle. FSHtetra plateaued at a high concentration from day 5 to 15, without a midcycle peak. There were lower concentrations of LHdi than LHtri, except at midcycle when the opposite occurred. The mean numbers of SA and SU residues per molecule of FSH and LH in serum showed four different patterns during the cycle, all with highly significant (P < 0.0001) differences between levels at different phases of the cycle. The pattern of SA residues on FSH was 'M'-shaped, and that of SU on LH 'V'-shaped. Conclusion. Serum FSH and LH governing the natural ovarian stimulation process exhibited dynamic changes of glycosylation and glycan composition. This new information on the FSH and LH molecular structures may lead to more successful mono-ovulatory treatment regimens for ovulation induction in anovulatory women.
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| 16. |
- Wide, Leif, et al.
(författare)
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Effects of 17 beta-oestradiol and norethisterone acetate on sulfonation and sialylation of gonadotrophins in post-menopausal women
- 2010
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 115:2, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- Background. The number of terminal sialic acid and sulfonated N-acetylgalactosamine (SO3-GalNAc) on gonadotrophins in serum varies during the menstrual cycle and changes at menopause, suggesting that gonadal steroids modify their oligosaccharide synthesis. Our objective was to determine the effects of 17 beta-oestradiol (E-2) and a progestogen, norethisterone acetate (NETA), on the sulfonation and sialylation of gonadotrophins in post-menopausal women. Methods. Serum samples were obtained from eight post-menopausal women treated with 20 mg E-2 implants every 6 months, from four women who in addition were treated daily with 5 mg NETA orally for a 2-week period, and from four women who got this NETA treatment during a 4-week period. Sera from 11 non-treated post-menopausal women served as a reference group. The gonadotrophin serum concentrations, the number of SO3-GalNAc and sialic acid residues per serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) molecule, and the distributions of molecules with 0-1-2-3-4 sulfonated residues were measured. Results. The E-2-treated post-menopausal women had considerably less (P < 0.001) sialic acid and slightly more (P < 0.01) SO3-GalNAc per serum LH and FSH molecule than the non-treated. Two weeks of NETA treatment increased the sulfonation of LH (P < 0.01) and FSH (P < 0.05) concomitantly with decreased (P < 0.05) sialylation of LH. Conclusion. The primary effect of E-2 treatment was a decrease in sialylation and, due to competition for the same substrate, a secondary and consequentially minor increase in sulfonation of LH and FSH. The primary effect of the NETA therapy was an increase in the sulfonation of LH and FSH concomitantly with secondary and consequentially decreases in sialylation of LH.
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| 17. |
- Wide, Leif, et al.
(författare)
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Low- and Fully N-Glycosylated Gonadotropins Circulating in Women With Polycystic Ovary Syndrome
- 2021
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Ingår i: Journal of the Endocrine Society. - : ENDOCRINE SOC. - 2472-1972. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- Context: A preponderance of basic luteinizing hormone (LH) molecules having elevated bioactivity was detected in the circulation of women with polycystic ovary syndrome (PCOS). Subsequent studies have shown that LH and follicle-stimulating hormone (FSH) both circulate as glycoforms differing in number of glycans: low-N-glycosylated glycoforms, LHdi and FSHtri, with high in vitro bioactivity, and fully glycosylated glycoforms, LHtri and FSHtetra, with high in vivo bioactivity.Objective: This work aims to characterize the glycosylation patterns on circulating gonadotropin glycoforms in women with PCOS.Methods: Serum samples, collected from 8 women with PCOS were included. The concentration, sulfonation, and sialylation of each glycoform were determined and compared with values of serum samples from healthy women: 22 women at follicular phase, 16 at midcycle, and 15 after menopause.Results: All the women with PCOS had higher LHdi serum levels compared with those in the follicular-phase group. Median LHdi and median LHtri levels were significantly elevated in PCOS women. The percentage of LHdi was increased from 37 to 49 and that of FSHtri was decreased from 41 to 33. The LHdi, LHtri, and FSHtetra glycoforms were more sialylated and both LH glycoforms less sulfonated in women with PCOS.Conclusion: All women with PCOS had increased serum levels of LHdi, compared with those in the follicular phase. The percentage of LHdi was increased and that of FSHtri decreased in women with PCOS. The increased LHdi leads to maintenance of the abnormal early follicular development of the polycystic ovary, and the decreased FSHtri contributes to the arrested follicle growth.
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| 18. |
- Wide, Leif, et al.
(författare)
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Low-glycosylated forms of both FSH and LH play major roles in the natural ovarian stimulation
- 2018
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 123:2, s. 100-108
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Tidskriftsartikel (refereegranskat)abstract
- Background: The natural ovarian stimulation is mediated by four gonadotrophin glycoforms: FSHtri with three, FSHtetra with four, LHdi with two, and LHtri with three N-glycans. The aim of the study was to determine the serum concentrations of the four glycoforms and their contents of anionic monosaccharides (AMS), i.e. sialic acid (SA) and sulfonated N-acetylgalactosamine (SU) residues throughout the menstrual cycle. Methods: Serum samples were collected from 78 healthy women with regular menstrual cycles. The serum glycoform molecules were identified by their distributions at electrophoreses. Analyses were also performed after removal of terminal SA. The hormones were measured with time-resolved sandwich fluoroimlooimm u noassays. Results: The concentration profiles of the four glycoforms were markedly different. FSHtri, which had a 3-fold higher biopotency than FSHtetra, had peak levels on cycle day 5 and at midcycle and nadirs on cycle days 9 and 21-23. FSHtetra had a raised level on cycle days 5-12, followed by a decrease. LHdi and LHtri had similar patterns, but the peak/nadir ratio was much more pronounced for LHdi than for LHtri, 18 versus 4. The numbers of SA residues per molecule were at a maximum around midcycle when the corresponding numbers of SU were at a minimum. The SU/SA ratio was at a minimum on cycle day 12. Conclusion: The results indicate that the LHdi and the FSHtri molecules play major roles in the natural ovarian stimulation. The SU/SA ratios per molecule favoured a prolonged circulatory half-life of all glycoforms at the midcycle phase. The observations may lead to more successful inductions of ovulation in anovulatory women.
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| 19. |
- Wide, Leif, et al.
(författare)
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Molecular size and charge as dimensions to identify and characterize circulating glycoforms of human FSH, LH and TSH
- 2017
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 122:4, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Background: FSH, LH, and TSH are glycoprotein hormones secreted from the pituitary as fully and low-asparagine-glycosylated hormones. These glycoforms of the hormones exist as a large number of isoforms varying in their glycan contents of terminal anionic monosaccharides (AMS), i.e. sialic acid (SA) and sulfonated N-acetylgalactosamine (SU). Due to the immense heterogeneity and the low concentrations in serum it has been a challenge to develop reliable analytical methods to measure and characterize the circulating glycoforms of these hormones. Methods: The hormones were separated with respect to AMS content per molecule by calibrated 0.1% agarose suspension electrophoreses. Glycoforms in separated fractions were then analyzed with respect to size by 180 calibrated Sephadex G-100 gel filtrations. The hormones were measured with timeresolved sandwich fluoroimmunoassays. All separations and assays were performed in veronal buffer at pH 8.7. Sera and fractions were also analyzed after removal of terminal SA. Results: In addition to the fully glycosylated FSH, LH, and TSH, also tri-glycosylated FSH and di-glycosylated LH and TSH forms could be identified in serum samples. The low-and fully glycosylated hormones differed both with respect to size and to median number of AMS per molecule. Algorithms, based on the distributions by electrophoreses, were developed for each hormone to estimate percent low-glycosylated forms in serum. The median numbers of SA and SU per glycoform molecule were estimated using results obtained after desialylation. Conclusion: The methods can be used for identification and characterization of glycoforms of circulating FSH, LH, and TSH in physiological and clinical studies.
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| 20. |
- Wide, Leif, et al.
(författare)
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Serum half-life of pituitary gonadotropins is decreased by sulfonation and increased by sialylation in women
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:3, s. 958-64
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The gonadotropins are secreted from the human pituitary as spectra of isoforms with different degrees of sulfonation and sialylation of the oligosaccharides, modifications suspected to determine their half-lives in the circulation. OBJECTIVES: Our objectives were to determine the isoform composition of the serum gonadotropins during GnRH receptor blockade, and to estimate the half-lives in circulation of isoforms with 0-1-2-3 sulfonated N-acetylgalactosamine (SO(3)-GalNAc) residues. DESIGN/PARTICIPANTS: Serum samples were collected in seven healthy women before and up to 20 h after administration of the NAL-GLU GnRH antagonist. MAIN OUTCOME MEASURES: The number of sialic acid and SO(3)-GalNAc residues per LH and FSH molecule and the distribution of molecules with 0-1-2-3 sulfonated residues were measured. The half-lives were estimated by monoexponential decay. RESULTS: More sialylated and less sulfonated gonadotropin isoforms remain longer in circulation during GnRH receptor blockade. LH isoforms with two and three sulfonated residues per molecule had shorter half-lives compared with those with zero and one (109 and 80 vs. 196 and 188 min; P < 0.01). FSH isoforms with one and two sulfonated residues had shorter half-lives than those with zero (485 and 358 vs. 988 min; P < 0.01). CONCLUSIONS: The decline in LH and FSH during GnRH receptor blockade is associated with a decrease in sulfonated and increase in sialylated residues. The rapid disappearance of LH isoforms with two and three SO(3)-GalNAc residues suggests their removal by hepatic SO(3)-GalNAc-receptors similar to those in rodents. Episodical secretion of spectra of isoforms with different half-lives is expected to lead to continuous changes in gonadotropin isoform compositions in blood.
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| 21. |
- Wide, Leif, et al.
(författare)
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Sulfonation and sialylation of gonadotropins in women during the menstrual cycle, after menopause, and with polycystic ovarian syndrome and in men
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:11, s. 4410-4417
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Tidskriftsartikel (refereegranskat)abstract
- Context: More basic isoforms of LH and FSH appear in blood at midcycle and more acidic after menopause. The LH isoforms are more basic in women with polycystic ovarian syndrome (PCOS). These charge alterations may reflect differences in the number of two negatively charged residues on the gonadotropins: sialic acid and sulfonated N-acetylgalactosamine, residues that modulate the half-life of the gonadotropins in blood. Objective: The objective of the study was to determine the contributions of sialic acid and sulfonated N-acetylgalactosamine and sialic acid on LH and FSH to the observed alterations in charge. Design/Participants: Serum samples were obtained from 59 young women with regular cycles, nine postmenopausal women, 12 women with PCOS, and 40 young men. Main Outcome Measures: The number of sulfonated N-acetylgalactosamine and sialic acid residues per LH and FSH molecule in serum and the distributions of molecules with 0-1-2-3-4 sulfonated residues were determined by electrophoretic analyses before and after removal of sialic acid. Results: Considerably decreased sulfonation of LH was found at midcycle and in women with PCOS concomitant with slightly increased sialylation. The sulfonation of LH increased in the luteal phase, and the sialylation was highest after menopause for both hormones. The frequencies of sulfonated LH and FSH isoforms were directly related (P < 0.01) to body mass index in women with PCOS. Conclusion: The observed variations in sialic acid and sulfonated residues on serum gonadotropins are suggested to reflect alterations in the isoform composition of the hormones secreted by the pituitary, resulting in modulations of their biological properties, such as half-life in blood.
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| 22. |
- Wide, Leif, et al.
(författare)
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The common genetic variant of luteinizing hormone has a longer serum half-life than the wild type in heterozygous women
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:1, s. 383-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The common genetic variant of human LH has two mutations and an extra N-linked oligosaccharide chain, a modification expected to affect the half-life in the circulation. OBJECTIVES: Our objectives were to determine the half-lives of variant and wild-type forms of LH during GnRH receptor blockade in heterozygous women and to determine the time-related changes in isoform composition. DESIGN AND PARTICIPANTS: Serum samples were obtained from three healthy women heterozygous for variant LH before and up to 20 h after administration of the NAL-GLU GnRH antagonist. MAIN OUTCOME MEASURES: The half-lives were estimated by monoexponential decay. The number of sialic acid and sulfonated N-acetylgalactosamine residues per wild-type and variant LH molecule and the distribution of molecules with zero, one, two, or three sulfonated residues were measured. RESULTS: The variant LH had a half-life that was approximately 40% longer than the corresponding forms of wild-type LH (148 vs. 108 min; P < 0.001). Variant LH had more sialic acid residues per molecule than wild type (3.6 vs. 2.4; P < 0.05), whereas the number of sulfonated residues was similar (1.0 vs. 0.98). The decline in the variant LH during GnRH receptor blockade was associated with a decrease in sulfonated and an increase in sialic acid residues similar to that for in wild-type LH. Isoforms of either variant or wild-type LH with two to three sulfonate groups per molecule had the shortest half-life. CONCLUSION: Variant LH remains longer in circulation than wild type during GnRH receptor blockade in heterozygous women, in accord with its higher content of sialic acid.
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| 23. |
- Wide, Leif, et al.
(författare)
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Thyrotropin N-glycosylation and Glycan Composition in Severe Primary Hypothyroidism
- 2021
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Ingår i: Journal of the Endocrine Society. - : Endocrine Society. - 2472-1972. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Context: In severe primary hypothyroidism (sPH), the serum thyrotropin (TSH) levels are elevated with an increased degree of sialylation. The circulating TSH comprises 2 different TSH glycoforms: TSHdi with 2 and TSHtri with 3 N-glycans and methods have developed to determine their contents of anionic monosaccharides (AMS), that is, sialic acid (SA) and sulfonated N-acetylglactosamine (SU) residues.Objective: Characterize N-glycosylation and glycan composition of circulating TSH molecules and determine the effects during levothyroxine treatment in patients with sPH.Methods: Serum samples were obtained from 25 patients with sPH, from 159 euthyroid individuals, and from 12 women during treatment with levothyroxine for sPH. Degrees of N-glycosylation and concentrations of TSHdi and TSHtri as well as their contents of AMS, SA, and SU residues were determined. Results: The circulating TSH molecules in sPH patients had lower degrees of N-glycosylation, higher degrees of sialylation, and lower degrees of sulfonation than in euthyroid individuals. Levothyroxin restored sialylation and sulfonation of the glycans already at low free thyroxine (FT4) levels, while degree of N-glycosylation was not restored until the FT4 levels were normal.Conclusions: The majority of TSH molecules in severe primary hypothyroidism were less N- glycosylated, more sialylated, and less sulfonated compared with euthyroid individuals. This glycan pattern favors a prolonged half-life in the circulation combined with lower in vitro biopotency at the target cells. During levothyroxine treatment of sPH patients, the sialylation and sulfonation of glycans were restored already at low FT4 levels, while N-glycosylation of TSH was not restored until the FT4 levels were normal.
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| 24. |
- Wide, Leif, et al.
(författare)
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Unique Pattern of N-Glycosylation, Sialylation, and Sulfonation on TSH Molecules in Serum of Children Up to 18 Months
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 104:10, s. 4651-4659
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Tidskriftsartikel (refereegranskat)abstract
- Context: N-glycosylation and glycan composition of human TSH molecules modulate the biological properties of TSH in different physiological and clinical situations. The degree of sialylation of serum TSH was reported to be very low in normal third-trimester fetuses compared with normal adults. The circulating TSH glycoforms and their glycan compositions in young children have hitherto not been determined.Objective: To characterize N-glycosylation and glycan composition of circulating TSH molecules in young children.Design, Participants, Main Outcome Measures: Serum samples were obtained from euthyroid individuals: 33 children, age 2 weeks to 3 years, and 264 adults. The di-glycosylated TSH and tri-glycosylated TSH glycoforms were determined and characterized with respect to sialylation and sulfonation. The TSH N-glycosylation was also examined in pituitary extracts of 75 individuals.Results: In children up to 18 months of age, most TSH molecules were low-N-glycosylated, high-sulfonated, and low-sialylated compared with older children and adults. The degree of N-glycosylation was similar in serum and pituitary extracts up to 3 months of age and after that was higher in serum than in pituitary extracts.Conclusions: Children up to age 18 months had low-sialylated TSH molecules, similar to those reported for third-trimester fetuses. Most TSH molecules in young children were of smaller size and less negatively charged, favoring transport into their target tissues. The low sialylation favors a high biopotency at thyroid and extrathyroidal TSH receptors. A delayed development of the liver SO3-N-acetylgalactosamine receptor function after birth is a likely explanation of the highly sulfonated TSH molecules in serum samples of infants.
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| 25. |
- Wuu, J., et al.
(författare)
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Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China
- 2002
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Ingår i: European Journal of Cancer Prevention. - : Ovid Technologies (Wolters Kluwer Health). - 0959-8278 .- 1473-5709. ; 11:3, s. 283-293
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.
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| 26. |
- Xu, B., et al.
(författare)
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Maternal and gestational correlates of pregnancy prolactin and growth hormone in USA and China
- 2003
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Ingår i: European Journal of Cancer Prevention. - : Ovid Technologies (Wolters Kluwer Health). - 0959-8278 .- 1473-5709. ; 12:1, s. 35-42
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent, prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other.
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